Gillis H L, Lutchen K R
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
J Appl Physiol (1985). 1999 Jun;86(6):2001-12. doi: 10.1152/jappl.1999.86.6.2001.
Although airway remodeling and inflammation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflammation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction.
虽然哮喘中的气道重塑和炎症可增强单个气道的收缩反应，但其对整个气道网络结构变化的影响尚不清楚。我们提出了一种人体肺部形态计量模型，该模型纳入了健康、轻度和重度哮喘气道中外膜、气道平滑肌（ASM）和黏膜对应的横截面积以及实质束缚的影响。施加异质性的ASM百分比缩短刺激，会导致健康气道和哮喘气道出现不同的收缩模式。我们计算了0.1至5赫兹的肺阻力和弹性。我们发现，对于给定的ASM刺激，哮喘患者的壁面积分布不仅会放大肺周边收缩的平均值，还会放大其异质性。此外，在健康肺部只会产生轻微变化的异质性ASM缩短，在哮喘肺部典型呼吸频率下可导致肺阻力和弹性的高反应性变化，即使气道阻力增加相对较小。当肺周边随机出现气道闭合时就会出现这种情况。我们认为异质性是哮喘高反应性的关键决定因素，急性哮喘更多是广泛气道壁炎症和重塑的结果，使肺部易于产生异质性收缩的急性模式。
